The proposed program will encompass three main areas of investigation: 1. The structure of the various classes and subclasses of immunoglobulins in an effort to relate this to their specific functional properties, their evolutionary origins and their genetic controls. 2. Possible mechanisms by which cryoglobulins with rheumatoid factor activity can cause tissue damage. 3. The chemical and immunological characterization of amyloid and mechanisms for its deposition and formation.